Although there is growing evidence for continuities in adolescent and adult depression, with similarities in clinical presentation and natural history, maturational differences also have been highlighted. Specifically, several studies reported greater variations in electroencephalographic (EEG) sleep changes, hypothalamic- pituitary-adrenal (HPA) activity and antidepressant (AD) response in depressed adolescents compared with the findings in adults. This proposal aims to understand the mechanism(s) underlying these developmental differences and to develop a strategy for use in identifying those patients, both youngsters and adults, who might benefit from AD treatment in general, and from bupropion treatment in particular. Based on the results of preliminary studies conducted in our laboratory, this investigation proposes to predict AD response to sustained-release bupropion in depressed adolescents and adults by assessing rapid eye movement (REM) sleep and HPA activity responses to single-dose bupropion administration prior to initiating treatment. Following completion of the sleep and neuroendrocrine assessments, subjects will receive clinical treatment with sustained-release bupropion for 8 weeks. In addition to examining the strength of association between REM sleep (and HPA) response to the bupropion challenge and clinical response to the drug, psychosocial measures (specifically stressful life experiences and social support) will be obtained in order to assess their contribution to AD response, both singly and in combination with the neurobiological measures. Bupropion was selected specifcally because of its relatively subtle effects on REM sleep compared with the other AD compounds (tricyclic agents and selective serotonin reuptake inhibitors, in particular). The robust REM sleep suppression induced by the other AD compounds might mask inter-individual variability; inherent differences in sensitivity that relate to treatment response could be lost due to a ceiling effect. Adolescent depression is a major public health problem that not only relates to the younger population, but also for the long-term mental health and social functioning of adults. Because depression in youngsters is associated with serious morbidity and mortality, and since it marks the gateway into recurrent mood disorders in a large proportion of adults, the early identification and effective treatment of depression in youngsters is of utmost importance. Because the long-term effects of AD agents on the developing human brain are not known, and because initial treatment can influence subsequent treatment compliance and clinical course, the identification of depressed youth who would (or would not) benefit from treatment with AD drugs is crucial. Results of the proposed study should not only be helpful in developing novel and more effective AD drugs and treatment strategies for youngsters, but also will enhance our understanding of the neurobiology of inadequate AD response in some adult patients with depression.